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1.
Drug Chem Toxicol ; 36(4): 412-20, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23742174

RESUMO

2,3,3,3-Tetrafluoropropene (HFO-1234yf) is being developed as a refrigerant because it has a very low global warming potential (less than 10), as contrasted to the hydrofluorocarbons, which is intended to replace with values of over 500. Several toxicology studies were conducted to develop a toxicology profile for this material. There was no lethality in mice and rats receiving single 4-hour exposures up to 101,850 or 405,800 ppm, respectively. Additionally, there was no mortality or clinical signs of toxicity when rabbits were exposed to 100,000 ppm for 1 hour. Exposures up to 120,000 ppm did not induce cardiac sensitization to adrenalin in dogs. Rats were exposed to HFO-1234yf at levels of 5000, 20,000 and 50,000 ppm 6 hours/day 5 days/week for 2 weeks and at levels of 5000, 15,000 and 50,000 ppm for 4 weeks and for 90 days. No treatment-related adverse effects were noted in these studies. HFO-1234yf was not genotoxic in a mouse and a rat micronucleus assay, and unscheduled DNA synthesis assay and was not clastogenic in human lymphocytes. HFO-1234yf was mutagenic to Salmonella typhimurium TA 100 and Escherichia coli (WP2 uvrA) at concentrations of 20% and higher in the presence of metabolic activation only. There were no biologically significant effects in a rat developmental toxicity study with exposures up to 50,000 ppm.


Assuntos
Aberrações Cromossômicas/induzido quimicamente , Escherichia coli/efeitos dos fármacos , Fluorocarbonos/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Animais , Testes de Provocação Brônquica , Replicação do DNA/efeitos dos fármacos , Cães , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Camundongos , Testes para Micronúcleos , Coelhos , Ratos , Ratos Sprague-Dawley , Refrigeração/métodos , Fatores de Tempo , Toxicologia/métodos
2.
Drug Chem Toxicol ; 36(2): 170-80, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22486185

RESUMO

HFO-1234ze is being developed as a refrigerant, propellant, and foam-blowing agent because it has a very low global warming potential (less than 10), as contrasted to the hydrofluorocarbons with values of over 500. Several toxicology studies were conducted to develop a toxicology profile for this material. There was no lethality in mice and rats receiving single 4-hour exposures up to 103,300 or 207,000 ppm, respectively. Exposures up to 120,000 ppm did not induce cardiac sensitization to adrenalin. Rats were exposed to HFO-1234ze at levels of 5,000, 20,000, and 50,000 ppm 6 hours/day 5 days/week for 2 weeks. Predominate findings of increased liver and kidney weights and histopathological changes in the liver and heart suggested that these organs were the targets for HFO-1234ze toxicity. In a 4-week study at 1000, 5000, 10,000, and 15,000 ppm, the only organ showing treatment-related effects was the heart. In a 90-day study with exposures of 1500, 5000, and 15,000 ppm 6 hours/day 5 days/week, again, the heart was the only target organ. The findings consisted of focal and multifocal mononuclear cell infiltrates in the heart. There was no evidence of fibrosis, and, when compared to the 2- and 4-week studies, there did not appear to be an increase in severity with length of exposure. HFO-1234ze was inactive in a mouse and rat micronucleus assay, an Ames assay, and an unscheduled DNA synthesis assay and was not clastogenic in human lymphocytes. It was also not a developmental toxin in either the rat or rabbit, even at exposure levels up to15,000 ppm.


Assuntos
Propelentes de Aerossol/toxicidade , Fluorocarbonos/toxicidade , Testes de Toxicidade/métodos , Administração por Inalação , Propelentes de Aerossol/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Feminino , Fluorocarbonos/administração & dosagem , Aquecimento Global , Coração/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Coelhos , Ratos , Ratos Sprague-Dawley , Especificidade da Espécie , Fatores de Tempo
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